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Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
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Host AMPK Is a Modulator of Plasmodium Liver Infection

Margarida T Grilo Ruivo1, Iset Medina Vera1, Joana Sales-Dias1

  • 1Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.

Cell Reports
|August 30, 2016
PubMed

Insights

Malaria parasites suppress host AMP-activated protein kinase (AMPK) activity for replication. Overactive AMPK hinders Plasmodium growth, suggesting AMPK signaling as a target for antimalarial therapies.

Area of Science:

  • Cellular biology
  • Parasitology
  • Host-pathogen interactions

Background:

  • AMP-activated protein kinase (AMPK) regulates cellular energy homeostasis.
  • Most intracellular pathogens activate host AMPK for replication.
  • The role of AMPK in malaria parasite infection is not fully understood.

Purpose of the Study:

  • To investigate the role of host AMPK activity in Plasmodium infection of hepatic cells.
  • To determine if AMPK modulation can be a therapeutic strategy against malaria.

Main Methods:

  • Studied AMPK activity in hepatic cells infected with rodent malaria parasites.
  • Assessed the impact of AMPK modulation on Plasmodium growth and replication.
  • Utilized mouse models with activated AMPK function.

Main Results:

  • Infection with rodent malaria parasites suppressed host AMPK activity in hepatic cells.
  • Suppressed AMPK activity was dispensable for parasite infection.
  • Elevated AMPK activity was detrimental to Plasmodium spp. growth, including Plasmodium falciparum.
  • Host AMPK activation in mice negatively impacted malaria infection.

Conclusions:

  • Host AMPK signaling acts as a suppressive pathway against Plasmodium hepatic infection.
  • AMPK represents a potential target for host-directed antimalarial interventions.

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